The migration of activated
antigen-specific immune cells to the target tissues of virus replication is controlled by the expression of adhesion molecules on the vascular endothelium that bind to
ligands on circulating lymphocytes. Here, we demonstrate that the adhesion pathway mediated by
vascular cell adhesion molecule 1 (VCAM-1) plays a role in regulating T-cell-mediated
inflammation and pathology in nonlymphoid tissues, including the central nervous system (CNS) during
viral infection. The ablation of
VCAM-1 expression from endothelial and hematopoietic cells using a loxP-Cre recombination strategy had no major effect on the induction or overall tissue distribution of
antigen-specific T cells during a systemic
infection with lymphocytic choriomeningitis virus (LCMV), except in the case of lung tissue. However, enhanced resistance to lethal LCM and the significantly reduced magnitude and duration of footpad swelling observed in
VCAM-1 mutant mice compared to B6 controls suggest a significant role for
VCAM-1 in promoting successful local inflammatory reactions associated with efficient viral clearance and even life-threatening immunopathology under particular
infection conditions. Interestingly, analysis of the infiltrating populations in the brains of intracerebrally infected mice revealed that
VCAM-1 deletion significantly delayed migration into the CNS of antigen-presenting cells (macrophages and dendritic cells), which are critical for optimal stimulation of migrating virus-specific CD8(+) T cells initiating a pathological cascade. We propose that the impaired migration of these accessory cells in the brain may explain the improved clinical outcome of
infection in
VCAM-1 mutant mice. Thus, these results underscore the potential role of
VCAM-1 in regulating the immune response and inflammatory reactions against
viral infections.